Diet and Lifestyle in a Prospective Study of Bladder Cancer Survivors

描述(申请人提供)：膀胱癌是美国十大最常见的癌症之一，每年导致超过60,000例新病例和10,000人死亡。大多数病例(70%-80%)是在早期被诊断出来的(称为非肌肉浸润性疾病)，但癌症通常会复发(50%-80%)，还有一部分进一步发展为肌肉浸润性疾病，存活率很低。由于这种明显的高复发率和进展性，患者接受膀胱镜检查和重复的经尿道操作，使膀胱癌成为最昂贵的疾病之一。十字花科蔬菜的摄入与降低患膀胱癌的风险和提高存活率有关，这可能部分归因于其独特的植物化学异硫氰酸酯(ITCs)。膳食ITCs具有多方面的抗癌机制，是一种很有前途的化学预防药物。我们先前的体外、体内和流行病学研究有力地支持了饮食中的ITCs和富含ITC的十字花科蔬菜在预防膀胱癌复发和进展以及改善预后方面发挥关键作用。最重要的是，通过人体内的代谢途径，口服的ITCs被迅速输送到膀胱并集中在尿液中，使膀胱癌成为其抗癌活动的最佳靶点。这项申请要求对凯撒永久北加州(KPNC)和南加州(KPSC)医疗保健计划中的1811名新诊断的非肌肉浸润性膀胱癌患者进行一项新的前瞻性队列研究。我们的目标是全面研究十字花科蔬菜的摄入与ITC代谢相关的基因多态在潜在减少疾病复发和进展以及提高膀胱内治疗效果方面的作用。我们建议研究：1)十字花科蔬菜摄入量与膀胱癌复发和进展的关系；2)ITC代谢基因多态性对十字花科蔬菜摄入量与膀胱癌复发和进展关系的修饰作用；3)十字花科蔬菜摄入量与治疗药物之间的相互作用对膀胱癌复发和进展的影响。此外，我们建议利用纵向问卷数据和银行生物样本建立最大的非肌肉浸润性膀胱癌患者的预期队列，用于未来对膀胱癌结果的进一步研究，包括生存和生活质量。膀胱癌是一种研究极少的疾病，因为它的发病率和复发率不成比例，临床治疗费用高，对生活质量有重大影响。这项在美国最大的综合医疗保健环境之一进行的拟议研究将首次调查DIT在疾病复发和进展中的作用，并考虑到基因特征，以确定谁将受益最大。考虑到十字花科蔬菜在美国的广泛供应，这项研究可能会对膀胱癌的预后产生直接影响。

DESCRIPTION (provided by applicant): Bladder cancer is one of the top ten most common cancers in the U.S., contributing to over 60,000 new cases and 10,000 deaths annually. The majority of cases (70-80%) are diagnosed at early stage (termed "non-muscle invasive"), yet the cancer typically recurs (50-80%), with a subset further progressing to muscle- invasive disease with poor survival. Due to this markedly high recurrence and progression, patients are followed intensively by cystoscopy with repeat transurethral manipulation, making bladder cancer one of the most costly diseases. Cruciferous vegetable intake has been associated with reduced risk of primary bladder cancer and improved survival, which might be partly attributable to their unique phytochemical isothiocyanates (ITCs). Dietary ITCs are promising chemopreventive agents with multi-faceted anti-cancer mechanisms. Our prior in vitro, in vivo, and epidemiologic studies strongly support dietary ITCs and ITC-rich cruciferous vegetables playing a key role in preventing bladder cancer recurrence and progression and improving prognosis. Above all, via metabolic pathways in humans, orally ingested ITCs are rapidly delivered to the bladder and concentrated in the urine, rendering bladder cancer the best target for their anti-cancer activities. This application requests to conduct a new prospective cohort study of 1,811 newly diagnosed non- muscle invasive bladder cancer patients in the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) Medical Care Programs. Our goal is to comprehensively examine the role of cruciferous vegetable intake, in conjunction with genetic polymorphisms related to ITC metabolism, in potentially reducing disease recurrence and progression, and increasing the efficacy of intravesical treatment. We propose to investigate: 1) the associations between cruciferous vegetable intake and bladder cancer recurrence and progression; 2) the modifying effect of polymorphisms of ITC-metabolizing genes on the associations between cruciferous vegetable intake and bladder cancer recurrence and progression; and 3) the effects of the interactions between cruciferous vegetable intake and therapeutic agents on bladder cancer recurrence and progression. Furthermore, we propose to establish the largest prospective cohort of non-muscle invasive bladder cancer patients with longitudinal questionnaire data and banked biospecimens for further future research of bladder cancer outcomes including survival and quality of life. Bladder cancer is an extremely understudied disease considering its disproportionate high incidence and recurrence, high cost of clinical management, and significant impact on quality of life. The proposed study within one of the largest U.S. integrated health care settings will be the first to investigate the role of dit in recurrence and progression of the disease, with genetic profiles taken into consideration to identify those who will benefit most. Considering the wide availability of cruciferous vegetables in the U.S., this study could have an immediate impact on bladder cancer prognosis.